This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


1yry

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (08:12, 25 October 2023) (edit) (undo)
 
(15 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1yry.gif|left|200px]]
 
-
{{Structure
+
==Crystal structure of human PNP complexed with MESG==
-
|PDB= 1yry |SIZE=350|CAPTION= <scene name='initialview01'>1yry</scene>, resolution 2.80&Aring;
+
<StructureSection load='1yry' size='340' side='right'caption='[[1yry]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
-
|SITE=
+
== Structural highlights ==
-
|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=MSG:7-METHYL-6-THIO-GUANOSINE'>MSG</scene>
+
<table><tr><td colspan='2'>[[1yry]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YRY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YRY FirstGlance]. <br>
-
|ACTIVITY= [http://en.wikipedia.org/wiki/Purine-nucleoside_phosphorylase Purine-nucleoside phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.1 2.4.2.1]
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
-
|GENE=
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSG:7-METHYL-6-THIO-GUANOSINE'>MSG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-
}}
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1yry FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yry OCA], [https://pdbe.org/1yry PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1yry RCSB], [https://www.ebi.ac.uk/pdbsum/1yry PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1yry ProSAT]</span></td></tr>
-
 
+
</table>
-
'''Crystal structure of human PNP complexed with MESG'''
+
== Disease ==
-
 
+
[https://www.uniprot.org/uniprot/PNPH_HUMAN PNPH_HUMAN] Defects in PNP are the cause of purine nucleoside phosphorylase deficiency (PNPD) [MIM:[https://omim.org/entry/613179 613179]. It leads to a severe T-cell immunodeficiency with neurologic disorder in children.<ref>PMID:3029074</ref> <ref>PMID:1384322</ref> <ref>PMID:8931706</ref>
-
 
+
== Function ==
-
==Overview==
+
[https://www.uniprot.org/uniprot/PNPH_HUMAN PNPH_HUMAN] The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate.<ref>PMID:2104852</ref>
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/yr/1yry_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1yry ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of nucleosides and deoxynucleosides, generating ribose 1-phosphate and the purine base, which is an important step of purine catabolism pathway. The lack of such an activity in humans, owing to a genetic disorder, causes T-cell impairment, and drugs that inhibit this enzyme may have the potential of being utilized as modulators of the immunological system to treat leukemia, autoimmune diseases, and rejection in organ transplantation. Here, we describe kinetics and crystal structure of human PNP in complex with 7-methyl-6-thio-guanosine, a synthetic substrate, which is largely used in activity assays. Analysis of the structure identifies different protein conformational changes upon ligand binding, and comparison of kinetic and structural data permits an understanding of the effects of atomic substitution on key positions of the synthetic substrate and their consequences to enzyme binding and catalysis. Such knowledge may be helpful in designing new PNP inhibitors.
Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of nucleosides and deoxynucleosides, generating ribose 1-phosphate and the purine base, which is an important step of purine catabolism pathway. The lack of such an activity in humans, owing to a genetic disorder, causes T-cell impairment, and drugs that inhibit this enzyme may have the potential of being utilized as modulators of the immunological system to treat leukemia, autoimmune diseases, and rejection in organ transplantation. Here, we describe kinetics and crystal structure of human PNP in complex with 7-methyl-6-thio-guanosine, a synthetic substrate, which is largely used in activity assays. Analysis of the structure identifies different protein conformational changes upon ligand binding, and comparison of kinetic and structural data permits an understanding of the effects of atomic substitution on key positions of the synthetic substrate and their consequences to enzyme binding and catalysis. Such knowledge may be helpful in designing new PNP inhibitors.
-
==Disease==
+
Kinetics and crystal structure of human purine nucleoside phosphorylase in complex with 7-methyl-6-thio-guanosine.,Silva RG, Pereira JH, Canduri F, de Azevedo WF Jr, Basso LA, Santos DS Arch Biochem Biophys. 2005 Oct 1;442(1):49-58. PMID:16154528<ref>PMID:16154528</ref>
-
Known diseases associated with this structure: Neutral lipid storage disease with myopathy OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=609059 609059]], Nucleoside phosphorylase deficiency, immunodeficiency due to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164050 164050]]
+
-
==About this Structure==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
1YRY is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YRY OCA].
+
</div>
 +
<div class="pdbe-citations 1yry" style="background-color:#fffaf0;"></div>
-
==Reference==
+
==See Also==
-
Kinetics and crystal structure of human purine nucleoside phosphorylase in complex with 7-methyl-6-thio-guanosine., Silva RG, Pereira JH, Canduri F, de Azevedo WF Jr, Basso LA, Santos DS, Arch Biochem Biophys. 2005 Oct 1;442(1):49-58. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16154528 16154528]
+
*[[Purine nucleoside phosphorylase 3D structures|Purine nucleoside phosphorylase 3D structures]]
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Purine-nucleoside phosphorylase]]
+
[[Category: Large Structures]]
-
[[Category: Single protein]]
+
[[Category: Basso LA]]
-
[[Category: Basso, L A.]]
+
[[Category: Canduri F]]
-
[[Category: Canduri, F.]]
+
[[Category: Pereira JH]]
-
[[Category: Jr., W F.de Azevedo.]]
+
[[Category: Santos DS]]
-
[[Category: Pereira, J H.]]
+
[[Category: Silva RG]]
-
[[Category: Santos, D S.]]
+
[[Category: De Azevedo Jr WF]]
-
[[Category: Silva, R G.]]
+
-
[[Category: MSG]]
+
-
[[Category: SO4]]
+
-
[[Category: crystallography]]
+
-
[[Category: drug design]]
+
-
[[Category: mesg]]
+
-
[[Category: purine nucleoside phosphorylase]]
+
-
[[Category: synchrotron]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:26:45 2008''
+

Current revision

Crystal structure of human PNP complexed with MESG

PDB ID 1yry

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1yry"
Personal tools